A Randomized, Double-Blind, Placebo-Controlled, Multicentre Study to Assess Haemodynamic Effects of Serelaxin in Patients With Acute Heart Failure

Study Questions:

Does serelaxin, a recombinant form of human relaxin-2, improve hemodynamics in patients admitted with acute heart failure (AHF)?

Methods:

This was a randomized, double-blind, placebo-controlled study of serelaxin in patients admitted with AHF. Relaxin-2 mediates material hemodynamic and systemic adaptations to increased intravascular volume of pregnancy. Serelaxin (30 mcg/kg/d for 20 hours) was administered to 34 patients, and 37 received placebo. Patients had to have a pulmonary capillary wedge pressure (PCWP) ≥18 mm Hg prior to randomization, and all received a standardized loop diuretic regimen. Patients treated with inotropes or with a systolic blood pressure (SBP) <115 mm Hg or a glomerular filtration rate (GFR) <30 ml/min/1.73 m2 were excluded. The primary endpoints included the peak change from baseline PCWP and cardiac index during the first 8 hours of infusion.

Results:

Mean (standard deviation) patient age was 68.6 (11.9) years, SBP was 131 (15.9) mm Hg, and left ventricular ejection fraction was 33.4 (13.7)%. At baseline, mean PCWP in the serelaxin and placebo groups was 26.2 (5.9) and 26.5 (5.2) mm Hg, respectively, and mean confidence interval was 2.4 (0.7) and 2.2 (0.6) L/min/m2, respectively (both p > 0.05). Following serelaxin infusion, peak PCWP decrease was 6.7 (0.59) mm Hg and 4.3 (0.60) mm Hg in the serelaxin and placebo groups, respectively (p = 0.004 for between-group comparison). Cardiac index increased 0.32 (0.05) and 0.30 (0.05) L/min/m2 in serelaxin versus controls (p = 0.79). Pulmonary vascular resistance dropped on average by 20.3 (9.9) dynes and increased by 18.7 (9.9) dynes in the serelaxin versus placebo groups (between-group, p = 0.006). Serious adverse events were more common in the placebo versus serelaxin group (22% vs. 9%).

Conclusions:

The authors concluded that administration of serelaxin to hemodynamically stable patients with AHF was associated with an improvement in congestion.

Perspective:

In the phase III clinical study, RELAX-AHF, serelaxin led to a reduction in dyspnea and all-cause mortality at 180 days in stable patients with AHF. The present study suggests that these findings may be due to improvements in congestion. Within just 8 hours, patients on a standardized diuretic regimen who received serelaxin had a statistically significant within-group (difference from baseline) and between-group (difference between placebo and treatment) reduction in wedge pressure and systemic and pulmonary vascular resistance without an increase in cardiac index. However, treatment differences were clinically small in magnitude (a mean difference of <3 mm Hg in wedge pressure and mean pulmonary artery pressure <4 mm Hg between treatment and placebo groups), making it hard to conclude that congestion improvement alone led to the improvements noted in mortality with serelaxin.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant

Keywords: Pulmonary Wedge Pressure, Ventricular Function, Left, Diuretics, Pulmonary Artery, Sodium Potassium Chloride Symporter Inhibitors, Dyspnea, Hemodynamics, Heart Transplantation, Heart Diseases, Heart Failure, Stroke Volume, Vascular Resistance, Glomerular Filtration Rate, Muscle Contraction


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